The added value of hypertonic saline solution to furosemide monotherapy in patients with acute decompensated heart failure: A meta‐analysis and trial sequential analysis

Abstract

We assessed the effects of hypertonic saline solution (HSS) plus furosemide versus furosemide alone in patients with acute decompensated heart failure (ADHF). We searched four electronic databases for randomized controlled trials (RCTs) until June 30, 2022. The quality of evidence (QoE) was assessed using the GRADE approach. All meta‐analyses were performed using a random‐effects model. A trial sequential analysis (TSA) was also conducted for intermediate and biomarker outcomes. Ten RCTs involving 3013 patients were included. HSS plus furosemide significantly reduced the length of hospital stay (mean difference [MD]: −3.60 days; 95% confidence interval [CI]: −4.56 to −2.64; QoE: moderate), weight (MD: −2.34 kg; 95% CI: −3.15 to −1.53; QoE: moderate), serum creatinine (MD: −0.41 mg/dL; 95% CI: −0.49 to −0.33; QoE: low), and type‐B natriuretic peptide (MD: −124.26 pg/mL; 95% CI: −207.97 to −40.54; QoE: low) compared to furosemide alone. HSS plus furosemide significantly increased urine output (MD: 528.57 mL/24 h; 95% CI: 431.90 to 625.23; QoE: moderate), serum Na+ (MD: 6.80 mmol/L; 95% CI: 4.92 to 8.69; QoE: low), and urine Na+ (MD: 54.85 mmol/24 h; 95% CI: 46.31 to 63.38; QoE: moderate) compared to furosemide alone. TSA confirmed the benefit of HSS plus furosemide. Due to the heterogeneity in mortality and heart failure readmission, meta‐analysis was not performed. Our study shows that HSS plus furosemide, compared to furosemide alone, improved surrogated outcomes in ADHF patients with low or intermediate QoE. Adequately powered RCTs are still needed to assess the benefit on heart failure readmission and mortality.

Dietary sodium and fluid intake in heart failure. A clinical consensus statement of the Heart Failure Association of the ESC

“…Several other studies and/or meta-analyses with hypertonic saline have reported similar results. [88][89][90][91][92] Conversely, the OSPREY-AHF (Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure) trial, conducted in acute congested HF cases requiring intravenous diuretics, reported that adding up to 6 g of oral NaCl per day on top of liberal Na + and fluid intake, compared to placebo, did not result in a significant difference in the combined endpoint of weight change and creatinine change at 96 h or discharge. 85 In conclusion, based upon the current studies, there is no convincing evidence for a clear benefit of the addition of hypertonic saline during the treatment of acute decompensated HF.…”